Effect of a-lipoic acid on vascular responses and nociception in diabetic rats

Norman E Cameron, Alison Margaret Jack, Mary Anne Cotter

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Oxidative stress contributes to the vascular and neurological complications of diabetes mellitus. The aim was to evaluate the effects of treatment with the radical scavenger and transition metal chelator, alpha -lipoic acid, on endothelium-dependent relaxation of the mesenteric vasculature and on superior cervical ganglion blood flow in 8 week streptozotocin-induced diabetic rats, alpha -lipoic acid effects on small nerve fiber-mediated nociception were also monitored. For the in vitro phenylephrine-precontracted mesenteric vascular bed, diabetes caused a 31% deficit in maximum endothelium-dependent relaxation to acetylcholine, and a 4-fold reduction in sensitivity. alpha -Lipoic acid gave 85% protection against these defects. Acetylcholine responses are mediated by nitric oxide and endothelium-derived hyperpolarizing factor: isolation of the latter by nitric oxide synthase blockade revealed a 74% diabetic deficit that was halved by alpha -lipoic acid. Superior cervical ganglion blood flow, 52% reduced by diabetes, was dose-dependently restored by ru-lipoic acid (ED50, 44 mg/kg/d). Diabetic rats exhibited mechanical and thermal hyperalgesia, which were abolished by alpha -lipoic acid treatment. Thus, diabetes impairs nitric oxide and endothelium-derived hyperpolarizing factor-mediated vasodilation. This contributes to reduced neural perfusion, and may be responsible for altered nociceptive function. The effect of alpha -lipoic acid strongly implicates oxidative stress in these events and suggests a potential therapeutic approach. (C) 2001 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)125-135
Number of pages10
JournalFree Radical Biology and Medicine
Volume31
Issue number1
DOIs
Publication statusPublished - Jul 2001

Keywords

  • diabetes mellitus
  • vascular endothelium
  • nitric oxide
  • EDHF
  • oxidative stress
  • mesenteric vasculature
  • autonomic nervous system
  • blood flow
  • pain
  • neuropathy
  • free radicals
  • ENDOTHELIUM-DEPENDENT RELAXATION
  • NERVE BLOOD-FLOW
  • ALDOSE REDUCTASE INHIBITION
  • MESENTERIC ARTERIAL BED
  • CORPUS CAVERNOSUM
  • NITRIC-OXIDE
  • OXIDATIVE STRESS
  • PERIPHERAL-NERVE
  • NEUROVASCULAR FUNCTION
  • LIPID-PEROXIDATION

Cite this

Effect of a-lipoic acid on vascular responses and nociception in diabetic rats. / Cameron, Norman E; Jack, Alison Margaret; Cotter, Mary Anne.

In: Free Radical Biology and Medicine, Vol. 31, No. 1, 07.2001, p. 125-135.

Research output: Contribution to journalArticle

Cameron, Norman E ; Jack, Alison Margaret ; Cotter, Mary Anne. / Effect of a-lipoic acid on vascular responses and nociception in diabetic rats. In: Free Radical Biology and Medicine. 2001 ; Vol. 31, No. 1. pp. 125-135.
@article{ac6b831fbf984a23b4e0668edd8e12d1,
title = "Effect of a-lipoic acid on vascular responses and nociception in diabetic rats",
abstract = "Oxidative stress contributes to the vascular and neurological complications of diabetes mellitus. The aim was to evaluate the effects of treatment with the radical scavenger and transition metal chelator, alpha -lipoic acid, on endothelium-dependent relaxation of the mesenteric vasculature and on superior cervical ganglion blood flow in 8 week streptozotocin-induced diabetic rats, alpha -lipoic acid effects on small nerve fiber-mediated nociception were also monitored. For the in vitro phenylephrine-precontracted mesenteric vascular bed, diabetes caused a 31{\%} deficit in maximum endothelium-dependent relaxation to acetylcholine, and a 4-fold reduction in sensitivity. alpha -Lipoic acid gave 85{\%} protection against these defects. Acetylcholine responses are mediated by nitric oxide and endothelium-derived hyperpolarizing factor: isolation of the latter by nitric oxide synthase blockade revealed a 74{\%} diabetic deficit that was halved by alpha -lipoic acid. Superior cervical ganglion blood flow, 52{\%} reduced by diabetes, was dose-dependently restored by ru-lipoic acid (ED50, 44 mg/kg/d). Diabetic rats exhibited mechanical and thermal hyperalgesia, which were abolished by alpha -lipoic acid treatment. Thus, diabetes impairs nitric oxide and endothelium-derived hyperpolarizing factor-mediated vasodilation. This contributes to reduced neural perfusion, and may be responsible for altered nociceptive function. The effect of alpha -lipoic acid strongly implicates oxidative stress in these events and suggests a potential therapeutic approach. (C) 2001 Elsevier Science Inc.",
keywords = "diabetes mellitus, vascular endothelium, nitric oxide, EDHF, oxidative stress, mesenteric vasculature, autonomic nervous system, blood flow, pain, neuropathy, free radicals, ENDOTHELIUM-DEPENDENT RELAXATION, NERVE BLOOD-FLOW, ALDOSE REDUCTASE INHIBITION, MESENTERIC ARTERIAL BED, CORPUS CAVERNOSUM, NITRIC-OXIDE, OXIDATIVE STRESS, PERIPHERAL-NERVE, NEUROVASCULAR FUNCTION, LIPID-PEROXIDATION",
author = "Cameron, {Norman E} and Jack, {Alison Margaret} and Cotter, {Mary Anne}",
year = "2001",
month = "7",
doi = "10.1016/S0891-5849(01)00564-0",
language = "English",
volume = "31",
pages = "125--135",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Effect of a-lipoic acid on vascular responses and nociception in diabetic rats

AU - Cameron, Norman E

AU - Jack, Alison Margaret

AU - Cotter, Mary Anne

PY - 2001/7

Y1 - 2001/7

N2 - Oxidative stress contributes to the vascular and neurological complications of diabetes mellitus. The aim was to evaluate the effects of treatment with the radical scavenger and transition metal chelator, alpha -lipoic acid, on endothelium-dependent relaxation of the mesenteric vasculature and on superior cervical ganglion blood flow in 8 week streptozotocin-induced diabetic rats, alpha -lipoic acid effects on small nerve fiber-mediated nociception were also monitored. For the in vitro phenylephrine-precontracted mesenteric vascular bed, diabetes caused a 31% deficit in maximum endothelium-dependent relaxation to acetylcholine, and a 4-fold reduction in sensitivity. alpha -Lipoic acid gave 85% protection against these defects. Acetylcholine responses are mediated by nitric oxide and endothelium-derived hyperpolarizing factor: isolation of the latter by nitric oxide synthase blockade revealed a 74% diabetic deficit that was halved by alpha -lipoic acid. Superior cervical ganglion blood flow, 52% reduced by diabetes, was dose-dependently restored by ru-lipoic acid (ED50, 44 mg/kg/d). Diabetic rats exhibited mechanical and thermal hyperalgesia, which were abolished by alpha -lipoic acid treatment. Thus, diabetes impairs nitric oxide and endothelium-derived hyperpolarizing factor-mediated vasodilation. This contributes to reduced neural perfusion, and may be responsible for altered nociceptive function. The effect of alpha -lipoic acid strongly implicates oxidative stress in these events and suggests a potential therapeutic approach. (C) 2001 Elsevier Science Inc.

AB - Oxidative stress contributes to the vascular and neurological complications of diabetes mellitus. The aim was to evaluate the effects of treatment with the radical scavenger and transition metal chelator, alpha -lipoic acid, on endothelium-dependent relaxation of the mesenteric vasculature and on superior cervical ganglion blood flow in 8 week streptozotocin-induced diabetic rats, alpha -lipoic acid effects on small nerve fiber-mediated nociception were also monitored. For the in vitro phenylephrine-precontracted mesenteric vascular bed, diabetes caused a 31% deficit in maximum endothelium-dependent relaxation to acetylcholine, and a 4-fold reduction in sensitivity. alpha -Lipoic acid gave 85% protection against these defects. Acetylcholine responses are mediated by nitric oxide and endothelium-derived hyperpolarizing factor: isolation of the latter by nitric oxide synthase blockade revealed a 74% diabetic deficit that was halved by alpha -lipoic acid. Superior cervical ganglion blood flow, 52% reduced by diabetes, was dose-dependently restored by ru-lipoic acid (ED50, 44 mg/kg/d). Diabetic rats exhibited mechanical and thermal hyperalgesia, which were abolished by alpha -lipoic acid treatment. Thus, diabetes impairs nitric oxide and endothelium-derived hyperpolarizing factor-mediated vasodilation. This contributes to reduced neural perfusion, and may be responsible for altered nociceptive function. The effect of alpha -lipoic acid strongly implicates oxidative stress in these events and suggests a potential therapeutic approach. (C) 2001 Elsevier Science Inc.

KW - diabetes mellitus

KW - vascular endothelium

KW - nitric oxide

KW - EDHF

KW - oxidative stress

KW - mesenteric vasculature

KW - autonomic nervous system

KW - blood flow

KW - pain

KW - neuropathy

KW - free radicals

KW - ENDOTHELIUM-DEPENDENT RELAXATION

KW - NERVE BLOOD-FLOW

KW - ALDOSE REDUCTASE INHIBITION

KW - MESENTERIC ARTERIAL BED

KW - CORPUS CAVERNOSUM

KW - NITRIC-OXIDE

KW - OXIDATIVE STRESS

KW - PERIPHERAL-NERVE

KW - NEUROVASCULAR FUNCTION

KW - LIPID-PEROXIDATION

U2 - 10.1016/S0891-5849(01)00564-0

DO - 10.1016/S0891-5849(01)00564-0

M3 - Article

VL - 31

SP - 125

EP - 135

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 1

ER -